Congestive heart failure (chf) medicinal chemistry

A condition in which the heart is unable to pump sufficient blood
to meet the metabolic demand of the body and also unable to receive it back because every time after a systole.

1. Congestive Heart Failure
(CHF)
1
Presented By-
Morankar. Tushar D.
(T.Y.B.Pharm)

Guided By-
Dr. Ghodage Mangesh G.

2. Content
▪Introduction
▪How Heart Failure Is Diagnosed
▪Treatment strategies of CHF GOAL
▪Classification..
▪Structure with IUPAC..
▪Mechanism of Action…
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3. Introduction
A condition in which the heart is unable to pump sufficient blood
to meet the metabolic demand of the body and also unable to receive it
back because every time after a systole.
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Mr.Morankar Tushar D.

4. Diagnosed
Echo
Chest X-ray
ECG
Blood tests
How Heart Failure Is Diagnosed
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Mr.Morankar Tushar D.

5. Treatment strategies of CHF GOAL
Increase cardiac output
Reduce preload and afterload
increase myocardial contractility.
Inotropic agents
β adrenergic agonist
β adrenergic antagonist
Vasodilators: Ca
2+
Channel Blocker
Diuretic agents
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6. Classification..
1. Inotropic drugs:
(a)Cardiac glycosides: Digoxin, Digitoxin
(b)Sympathomimetics: Dobutamine, Dopamine
(c) Phosphodiesterase III inhibitors: Amrinone
2. Diuretics:
(a) High ceiling diuretics: Furosemide, Bumetanide
(b) Thiazide like diuretics: Hydrochlorothiazide, Metolazone.
3. Inhibitors of Renin-Angiotensin system-
(a) ACE-inhibitors: Enalapril, Ramipril
(b) Angiotensin (AT receptor) antagonists: Losartan
4. Aldosterone antagonist- Spironolactone, Eplerenone
5. Vasodilators-
(a) Venodilators: Glyceryl trinitrate
(b) Arteriolar dilator: Hydralazine
(c) Arteriolar + Venodilator: Sod. Nitroprusside
IDIA-V
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7. Mechanism of Action of Digoxin
▪Inhibition of Na+/K ATPase pimp by
Digitalis
▪Increases Na+ concentration inside
the cell
▪Increases exchanges Na+ for ca++
▪Incresed intracellular Ca++
▪Incresed influx of Ca++ from
sarcoplasmic reticulum
▪Increases contractility of cardiac
muscles.
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8. Bosentan
4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)
-2-(pyrimidin-2- yl)pyrimidin-4-yl]benzene-1-sulfonamide
Bosentan is a competitive antagonist of endothelin-1 at
the endothelin-A (ET-A) and endothelin-B (ET-B) receptors.
Under normal conditions, endothelin-1 binding of ET-A
receptors causes constriction of the pulmonary blood
vessels.
Conversely, binding of endothelin-1 to ET-B receptors has
been associated with both vasodilation and
vasoconstriction of vascular smooth muscle, depending
on the ET-B subtype (ET-B1 or ET-B2) and tissue.
Bosentan blocks both ET-A and ET-B receptors, but is
thought to exert a greater effect on ET-A receptors,
causing a total decrease in pulmonary vascular
resistance
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9. Mechanism of Action…
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Normal
Endothelin -1 Endothelin -1
Endothelin –A Endothelin -B

Vasoconstriction Vasoconstriction Vasodilation
(Pulmonary Blood Vessels) (Vascular Smooth Muscles)
Bosentan
Mr.Morankar Tushar D.

10. Tezosentan
N-(2-(2-(2H-tetrazol-5-yl)pyridin-4-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)
pyrimidin-4-yl)-5-isopropylpyridine-2-sulfonamide
1
5
3
4
5
6
1
2
3
4
2
6
2
1
3
4
5
6
2
3
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5
6
1
2 3
4
5
2
Tezosentan is a non-selective ETA and ETB
receptor antagonist.
 It acts as a vasodilator and was designed
as a therapy for patients with acute heart
failure.
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11. Nesiritide
▪Nesiritide (Natrecor) is the
recombinant form of the 32 amino
acid human B-type natriuretic
peptide(BNP), which is normally
produced by the ventricular
myocardium.
▪Nesiritide works to facilitate
cardiovascular fluid homeostasis
through counter regulation of the
renin–angiotensin–aldosterone
system, stimulating cGMP, leading
to smooth muscle cell relaxation.
Vasodilation

NPR-A
BNP
GTP
cGMP
▪Recombinant human B-type natriuretic peptide (BNP)
Diuresis

Natriuresis

NO
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12. 17-Oct-19
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